INVESTIGATING THE SEX SPECIFIC RATES OF REPLICATION DRIVEN MUTATIONS IN HUMANS USING GENOME-WIDE INDEL MUTATIONS IN HUMAN ALU REPEATS

Background: To understand the tempo and mode of evolution at the nucleotide level it is important toestimate the spontaneous rate of each mutation type. Many molecular evolutionary studies have concluded thatdue to the greater number of cell divisions in the male germline than in the female germline, replication-basednucleotide substitutions in primates occur more frequently in males than in females. However, a potential sex biasin mutations other than nucleotide substitutions has not been extensively investigated. The human Alu repeatsprovide an ideal mechanism to further investigate the degree of replication-based indel (insertion and deletion)mutations in the human chromosomes. Results: We analyze patterns of small indel mutations (1bp) in the middlepoly (A) track of Alu repeats across the entire human genome in order to elucidate the processes of mutation andfixation. This analysis adds further support for the accumulation of more mutations in the Y chromosome comparedto the X chromosome. We report the male-to-female mutation ratio α in humans as ~1.5. Conclusion: Ourresults suggest that although small indel mutation may be primarily replication driven (as previous studies suggest)the observed value of α does not exceed the threshold necessary to conclude that contributions of replicationindependent factors are negligible. We also report that, with small indels (1bp) deletions outnumber insertionevents. This relative excess of deletions may be an important parameter in the long-term evolution of genomicsize.